tbuckley/cabot-search huggingface dataset:
Distinct pathophysiological pathways in women and men with heart failure
Authors: Alice Ravera, Bernadet T. Santema, Rudolf A. de Boer, Stefan D. Anker, Nilesh J. Samani, Chim C. Lang, Leong Ng, John G.F. Cleland, Kenneth Dickstein, Carolyn S.P. Lam, Harriette G. C. Van Spall, Gerasimos Filippatos, Dirk J. van Veldhuisen, Marco Metra, Adriaan A. Voors, Iziah E. Sama
Journal: European Journal of Heart Failure (2022)

Abstract Aims Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. Methods and results In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over‐representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up‐regulated in women, while 21/363 and 14/363 were up‐regulated in men. In both cohorts, the strongest up‐regulated biomarkers in women were leptin and fatty acid binding protein‐4, compared to matrix metalloproteinase‐3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over‐representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro‐inflammatory response in men (all p &lt; 0.0001). Conclusion In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro‐inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.
Circulating Tumor DNA–Based MRD Assessment in Patients with CLL Treated with Obinutuzumab, Acalabrutinib, and Venetoclax
Authors: Moritz Fürstenau, Jonathan Weiss, Adam Giza, Fabian Franzen, Sandra Robrecht, Anna-Maria Fink, Kirsten Fischer, Christof Schneider, Eugen Tausch, Stephan Stilgenbauer, Matthias Ritgen, Anke Schilhabel, Monika Brüggemann, Barbara Eichhorst, Michael Hallek, Paula Cramer
Journal: Clinical Cancer Research (2022)

With the advent of highly efficacious time-limited combination treatments of targeted agents in chronic lymphocytic leukemia (CLL), minimal residual disease (MRD) assessment has gained importance as a measure for therapeutic success and as a surrogate for progression-free survival. The currently most widely used method is multicolor flow cytometry, which detects circulating CLL cells in the peripheral blood. However, it seems to be less sensitive for the detection of MRD in the lymph node compartment.To evaluate whether a cell-free approach can overcome this limitation, we performed serial assessments of circulating tumor DNA (ctDNA) in patients with CLL treated with obinutuzumab, acalabrutinib, and venetoclax in the phase II CLL2-BAAG trial. Patient-specific variability, diversity, joining (VDJ) rearrangements as well as somatic driver mutations were tracked before, during and after treatment by digital droplet PCR in blood plasma. Furthermore, these were systematically compared to matched flow cytometry data.In the 381 sample pairs, ctDNA and flow cytometry yielded highly concordant results. However, clone-specific ctDNA was detected in 44 of 152 samples (29%) that were assessed as undetectable MRD (uMRD) by flow cytometry (defined as less than one CLL cell in 10,000 normal leukocytes). 29 ctDNA-negative samples showed detectable MRD >10-4 by flow cytometry. Also, somatic driver mutations were detected with a similar sensitivity compared with patient-specific VDJ rearrangements in plasma. In patients with predominantly nodal residual disease, ctDNA compared favorably with 4-color flow cytometry and seemed to more accurately reflect the entire disease burden across compartments.On the basis of these findings, ctDNA-based MRD assessment appears to be a promising method to complement cell-based MRD approaches like flow cytometry that focus on circulating CLL cells in the peripheral blood.
Anti-oxidant anti-inflammatory and antibacterial tannin-crosslinked citrate-based mussel-inspired bioadhesives facilitate scarless wound healing
Authors: Keke Wu, Meimei Fu, Yitao Zhao, Ethan Gerhard, Yue Li, Jian Yang, Jinshan Guo
Journal: Bioactive Materials (2022)

The revolutionary role of tissue adhesives in wound closure, tissue sealing, and bleeding control necessitates the development of multifunctional materials capable of effective and scarless healing. In contrast to the use of traditionally utilized toxic oxidative crosslinking initiators (exemplified by sodium periodate and silver nitrate), herein, the natural polyphenolic compound tannic acid (TA) was used to achieve near instantaneous (<25s), hydrogen bond mediated gelation of citrate-based mussel-inspired bioadhesives combining anti-oxidant, anti-inflammatory, and antimicrobial activities (3A-TCMBAs). The resulting materials were self-healing and possessed low swelling ratios (<60%) as well as considerable mechanical strength (up to ∼1.0 MPa), elasticity (elongation ∼2700%), and adhesion (up to 40 kPa). The 3A-TCMBAs showed strong in vitro and in vivo anti-oxidant ability, favorable cytocompatibility and cell migration, as well as photothermal antimicrobial activity against both Staphylococcus aureus and Escherichia coli (>90% bacterial death upon near-infrared (NIR) irradiation). In vivo evaluation in both an infected full-thickness skin wound model and a rat skin incision model demonstrated that 3A-TCMBAs + NIR treatment could promote wound closure and collagen deposition and improve the collagen I/III ratio on wound sites while simultaneously inhibiting the expression of pro-inflammatory cytokines. Further, phased angiogenesis was observed via promotion in the early wound closure phases followed by inhibition and triggering of degradation & remodeling of the extracellular matrix (ECM) in the late stage (supported by phased CD31 (platelet endothelial cell adhesion molecule-1) PDGF (platelet-derived growth factor) and VEGF (vascular endothelial growth factor) expression as well as elevated matrix metalloprotein-9 (MMP-9) expression on day 21), resulting in scarless wound healing. The significant convergence of material and bioactive properties elucidated above warrant further exploration of 3A-TCMBAs as a significant, new class of bioadhesive.
Organoids and regenerative hepatology
Authors: Nidhi Jalan‐Sakrikar, Teresa Brevini, Robert C. Huebert, Fotios Sampaziotis
Journal: Hepatology (2022)

The burden of liver diseases is increasing worldwide, with liver transplantation remaining the only treatment option for end‐stage liver disease. Regenerative medicine holds great potential as a therapeutic alternative, aiming to repair or replace damaged liver tissue with healthy functional cells. The properties of the cells used are critical for the efficacy of this approach. The advent of liver organoids has not only offered new insights into human physiology and pathophysiology, but also provided an optimal source of cells for regenerative medicine and translational applications. Here, we discuss various historical aspects of 3D organoid culture, how it has been applied to the hepatobiliary system, and how organoid technology intersects with the emerging global field of liver regenerative medicine. We outline the hepatocyte, cholangiocyte, and nonparenchymal organoids systems available and discuss their advantages and limitations for regenerative medicine as well as future directions.
IgA<sup>+</sup>memory B-cells are significantly increased in patients with asthma and small airway dysfunction
Authors: Anika Habener, Ruth Grychtol, Svenja Gaedcke, David DeLuca, Anna-Maria Dittrich, Christine Happle, Mustafa Abdo, Henrik Watz, Frauke Pedersen, Inke Regina König, Dominik Thiele, Matthias Volkmar Kopp, Erika von Mutius, Thomas Bahmer, Klaus Friedrich Rabe, Almut Meyer-Bahlburg, Gesine Hansen, Oliver Fuchs, Barbara Roesler, Nils Welchering, Naschla Kohistani-Greif, Johanna Kurz, Katja Landgraf-Rauf, Kristina Laubhahn, Nicole Maison, Claudia Liebl, Bianca Schaub, Markus Ege, Sabina Illi, Alexander Hose, Esther Zeitlmann, Mira Berbig, Carola Marzi, Christina Schauberger, Ulrich Zissler, Carsten Schmidt-Weber, Isabell Ricklefs, Gesa Diekmann, Lena Liboschik, Gesche Voigt, Laila Sultansei, Markus Weckmann, Gyde Nissen, Anne-Marie Kirsten, Benjamin Waschki, Christian Herzmann, Heike Biller, Karoline I. Gaede, Xenia Bovermann, Alena Steinmetz, Berrit Liselotte Husstedt, Catharina Nitsche, Vera Veith, Marlen Szewczyk, Folke Brinkmann, Aydin Malik, Nicolaus Schwerk, Christian Dopfer, Mareike Price, Adan Chari Jirmo, Bin Liu, Mifflin-Rae Calveron, Stefanie Weber, Svenja Foth, Chrysanthi Skevaki, Harald Renz, Meike Meyer, Tom Schildberg, Ernst Rietschel, Silke van Koningsbruggen-Rietschel, Miguel Alcazar
Journal: European Respiratory Journal (2022)

Background Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma. Methods In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models. Results Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild–moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgA + memory B-cells were associated with impaired lung function and specifically with parameters indicative for augmented resistance in the peripheral airways. Accordingly, asthma patients with small airway dysfunction (SAD) defined by impulse oscillometry showed increased frequencies of IgA + memory B-cells, particularly in patients with mild–moderate asthma. Additionally, IgA + memory B-cells significantly correlated with clinical features of SAD such as exacerbations. Conclusions With this study we demonstrate for the first time a significant association of increased IgA + memory B-cells with asthma and SAD, pointing towards future options for B-cell-directed strategies in preventing and treating asthma.
Erythrocytes are altered in pulmonary arterial hypertension
Authors: Etienne-Marie Jutant, Ly Tu, Raphaël Thuillet, Véronique Picard, Christophe Guignabert, Florence Parent, Olivier Sitbon, Marc Humbert, Laurent Savale, Alice Huertas
Journal: European Respiratory Journal (2022)

<b>Erythrocytes display structural and functional intrinsic defects in patients with pulmonary arterial hypertension. Their clinical relevance as potential biomarkers and their contribution in the disease pathophysiology still need to be defined.</b>https://bit.ly/3iDYFOe
Corticosteroids and superinfections in COVID-19 patients on invasive mechanical ventilation
Authors: Signe Søvik, Andreas Barratt-Due, Trine Kåsine, Theresa Olasveengen, Marianne Wigernes Strand, Anders Aune Tveita, Jan Erik Berdal, Martin Andreas Lehre, Torleif Lorentsen, Lars Heggelund, Tore Stenstad, Jetmund Ringstad, Fredrik Müller, Pål Aukrust, Jan Cato Holter, Ingvild Nordøy
Journal: Journal of Infection (2022)

To determine the incidence and characteristics of superinfections in mechanically ventilated COVID-19 patients, and the impact of dexamethasone as standard therapy.This multicentre, observational, retrospective study included patients ≥ 18 years admitted from March 1st 2020 to January 31st 2021 with COVID-19 infection who received mechanical ventilation. Patient characteristics, clinical characteristics, therapy and survival were examined.155/156 patients (115 men, mean age 62 years, range 26-84 years) were included. 67 patients (43%) had 90 superinfections, pneumonia dominated (78%). Superinfections were associated with receiving dexamethasone (66% vs 32%, p<0.0001), autoimmune disease (18% vs 5.7%, p<0.016) and with longer ICU stays (26 vs 17 days, p<0,001). Invasive fungal infections were reported exclusively in dexamethasone-treated patients [8/67 (12%) vs 0/88 (0%), p<0.0001]. Unadjusted 90-day survival did not differ between patients with or without superinfections (64% vs 73%, p=0.25), but was lower in patients receiving dexamethasone versus not (58% vs 78%, p=0.007). In multiple regression analysis, superinfection was associated with dexamethasone use [OR 3.7 (1.80-7.61), p<0.001], pre-existing autoimmune disease [OR 3.82 (1.13-12.9), p=0.031] and length of ICU stay [OR 1.05 p<0.001].In critically ill COVID-19 patients, dexamethasone as standard of care was strongly and independently associated with superinfections.
The paradox of immune checkpoint inhibition re-activating tuberculosis
Authors: Mohamed Ahmed, Liku B. Tezera, Paul T. Elkington, Alasdair J. Leslie
Journal: European Respiratory Journal (2022)

By attenuating T-cell activation, immune checkpoints (ICs) limit optimal anti-tumour responses and IC inhibition (ICI) has emerged as a new therapy for a broad range of cancers. T-cell responses are indispensable to tuberculosis (TB) immunity in humans. However, boosting T-cell immunity in cancer patients by blocking the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis can trigger re-activation of latent TB. This phenomenon appears to contradict the prevailing thought that enhancing T-cell immunity to Mycobacterium tuberculosis will improve immune control of this pathogen. In support of this anecdotal human data, several murine studies have shown that PD-1 deficiency leads to severe TB disease and rapid death. These observations warrant a serious reconsideration of what constitutes effective TB immunity and how ICs contribute to it. Through restraining T-cell responses, ICs are critical to preventing excessive tissue damage and maintaining a range of effector functions. Bolstering this notion, inhibitory receptors limit pathology in respiratory infections such as influenza, where loss of negative immune regulation resulted in progressive immunopathology. In this review, we analyse the mechanisms of ICs in general and their role in TB in particular. We conclude with a reflection on the emerging paradigm and avenues for future research.
Interspecific hybridization in tomato influences endogenous viral sRNAs and alters gene expression
Authors: Sara Lopez-Gomollon, Sebastian Y. Müller, David C. Baulcombe
Journal: Genome biology (2022)

Abstract Background Hybridization is associated with the activation of transposable elements and changes in the patterns of gene expression leading to phenotypic changes. However, the underlying mechanisms are not well understood. Results Here, we describe the changes to the gene expression in interspecific Solanum hybrids that are associated with small RNAs derived from endogenous (para)retroviruses (EPRV). There were prominent changes to sRNA profiles in these hybrids involving 22-nt species produced in the DCL2 biogenesis pathway, and the hybridization-induced changes to the gene expression were similar to those in a dcl2 mutant. Conclusions These findings indicate that hybridization leads to activation of EPRV, perturbation of small RNA profiles, and, consequently, changes in the gene expression. Such hybridization-induced variation in the gene expression could increase the natural phenotypic variation in natural evolution or in breeding for agriculture.
Development of patient decision aids for the treatment of lentigo maligna and low-risk basal cell carcinoma
Authors: Britney N. Wilson, Rohan Shah, Shenara Musthaq, Toral Vaidya, Thomas Bander, Hillary D. Johnson, Ian A. Maher, Christian L. Baum, Todd V. Cartee, Jonathan Cook, Terrence Cronin, Seemal R. Desai, Catherine C. DiGiorgio, Hayley Goldbach, Glenn Goldman, Shayna Gordon, Ann Haas, Nita Kohli, Geoffrey Lim, Alexander Miller, Eric A. Millican, Dennis A. Porto, Melissa Shive, Divya Srivastava, James Tidwell, Abigail Waldman, Monique Wilson, M. Laurin Council, Anthony M. Rossi
Journal: Journal of the American Academy of Dermatology (2022)
Extracorporeal life support as a bridge to lung transplantation strategy in anti-MDA5+ rapidly progressive interstitial lung disease is life-saving but with persistent difficulties at the bedside
Authors: Cloé Comarmond, Bruno Mégarbane
Journal: European Respiratory Journal (2022)

<b>Life-threatening presentation of anti-MDA5+ rapidly progressive interstitial lung disease requires early specific diagnosis to implement extracorporeal life support as a bridge to lung transplantation</b>https://bit.ly/3whD4BA
Impact of nonsegmental vitiligo on patients’ health-related quality of life in the United States
Authors: Shoshana R. Daniel, Kavita Gandhi, Kathryn P. Anastassopoulos, Amit G. Pandya, Vanja Sikirica, Reema Patel, Lynne Napatalung, Yuji Yamaguchi, Rebecca Baik, Khaled Ezzedine
Journal: British Journal of Dermatology (2022)

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Effects of sildenafil on symptoms and exercise capacity for heart failure with reduced ejection fraction and pulmonary hypertension (the <scp>SilHF</scp> study): a randomized placebo‐controlled multicentre trial
Authors: Trond J. Cooper, John G.F. Cleland, Marco Guazzi, Pierpaolo Pellicori, Tuvia Ben Gal, Offer Amir, Abdallah Al‐Mohammad, Andrew L. Clark, Alex McConnachie, Kjetil Steine, Kenneth Dickstein
Journal: European Journal of Heart Failure (2022)
Induced antibodies directed to the angiotensin receptor type 1 provoke skin and lung inflammation, dermal fibrosis and act species overarching
Authors: Xiaoyang Yue, Junping Yin, Xiaoqing Wang, Harald Heidecke, Alexander Maximilian Hackel, Xiaoru Dong, Brigitte Kasper, Lifang Wen, Liang Zhang, Kai Schulze-Forster, Juliane Junker, Hanna Grasshoff, Antje Müller, Gerd Wallukat, Ingolf Schimke, Julian Zeiner, Lisa Marie Deckstein, Nicole Mertens, Anja Kerstein-Staehle, Jennifer Elisabeth Hundt, Evi Kostenis, Xinhua Yu, Gabriela Riemekasten, Frank Petersen
Journal: Annals of the Rheumatic Diseases (2022)

To determine contributions and functions of autoantibodies (Abs) directed to the angiotensin receptor type 1 (AT1R), which are suggested to be involved in the pathogenesis of AT1R Abs-related diseases such as systemic sclerosis (SSc).
Quaternary nanoparticles enable sustained release of bortezomib for hepatocellular carcinoma
Authors: Ling Li, Yicheng Zhang, Yang Zhou, Haijie Hu, Yizong Hu, Christos Georgiades, Hai‐Quan Mao, Florin M. Selaru
Journal: Hepatology (2022)

Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related mortality in the world. Over the past two decades, there has been minimal improvement in therapies as well as clinical outcomes for patients with Barcelona Clinic Liver Cancer (BCLC)-B. These patients are treated with local interventions, including transarterial chemoembolization. Current methodologies only allow sustained intratumoral release measured in hours. Methodologies to allow sustained local release of the drug cargo over days to weeks are acutely needed. We hypothesize that tumor response as well as outcomes of patients with BCLC-B can be improved through utilization of a highly cytotoxic agent delivered with a sustained release platform.High-throughput drug screening across 40 HCC patient-derived organoids identified bortezomib (BTZ) as a highly cytotoxic small molecule for HCC. We designed and manufactured sustained release BTZ nanoparticles (BTZ-NP) using a flash nanocomplexation/nanoprecipitation process. We quantified the release profile and tested the anti-tumoral effects in vivo. The BTZ-NP formulation demonstrated a sustained release of BTZ of 30 days. This BTZ-NP formulation was highly effective in controlling tumor size and improved survival in vivo in three animal models of HCC, including when delivered via the hepatic artery, as we envision its delivery in patients. In addition, the BTZ-NP formulation was superior to treatment with doxorubicin-drug eluting beads.The BTZ-NP formulation provides a potent and safe treatment of HCC via a localized delivery approach. These results warrant additional preclinical studies to advance this technology to human clinical trials.
Severe pulmonary hypertension associated with COPD: long-term results of a prospective French multicentre cohort
Authors: Gaëlle Dauriat, Martine Reynaud-Gaubert, Vincent Cottin, Bouchra Lamia, David Montani, Drifa Belhadi, Marc Humbert, Cedric Laouenan, Hervé Mal
Journal: European Respiratory Journal (2022)

<b>This prospective study dealing with 99 incident patients followed over several years, without any patients lost to follow-up, confirms, with good-quality data, that the prognosis associated with severe PH-COPD is very poor</b>https://bit.ly/3DHjYIm
The Importance of Federal Action Supporting Overdose-Prevention Centers
Authors: Aneeqah H. Naeem, Corey S. Davis, Elizabeth A. Samuels
Journal: New England Journal of Medicine (2022)

Interview with Dr. Elizabeth Samuels on overdose-prevention centers and federal policy. (12:41)Download There is mounting interest among state and local officials in the United States in opening overdose-prevention centers, but there remains one fundamental barrier: the interpretation and enforcement of federal law.
Management of moderate to severe traumatic brain injury: an update for the intensivist
Authors: Geert Meyfroidt, Pierre Bouzat, Michael P. Casaer, Randall Chesnut, Sophie Rym Hamada, Raimund Helbok, Peter Hutchinson, Andrew I. R. Maas, Geoffrey Manley, David K. Menon, Virginia F. J. Newcombe, Mauro Oddo, Chiara Robba, Lori Shutter, Martin Smith, Ewout W. Steyerberg, Nino Stocchetti, Fabio Silvio Taccone, Lindsay Wilson, Elisa R. Zanier, Giuseppe Citerio
Journal: Intensive Care Medicine (2022)
When Naloxone Isn’t Enough
Authors: Sarah Messmer, Jennie Jarrett
Journal: New England Journal of Medicine (2022)

Interview with Dr. Elizabeth Samuels on overdose-prevention centers and federal policy. (12:41)Download Not all people who use drugs are interested in recovery support or medications for opioid use disorder. For patients who decline such care, the health care system does next to nothing to reduce the risk of death — but not because nothing can be done.
Cancer risk in severe alpha-1 antitrypsin deficiency: the importance of early identification
Authors: Adriana-Maria Hiller, Magnus Ekström, Eeva Piitulainen, Anne Lindberg, Eva Rönmark, Hanan Tanash
Journal: European Respiratory Journal (2022)

<b>Since individuals with severe alpha-1 antitrypsin deficiency may have an increased risk of developing cancer, and not only hepatic cancer, it is important to identify early and regularly follow-up these individuals</b> https://bit.ly/3LDr43S